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Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction

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Title
Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction
Author(s)
Jumee Kim; Kim, Somi; Lee, Seung-Yeon; Jo, Beom-Ki; Oh, Ji-Young; Kwon, Eun-Ji; Kim, Keun-Tae; Adpaikar, Anish Ashok; Kim, Eun-Jung; Jung, Han-Sung; Kim, Hwa-Ryeon; Roe, Jae-Seok; Hong, Chang Pyo; Kim, Jong Kyoung; Bon-Kyoung Koo; Cha, Hyuk-Jin
Publication Date
2023-11
Journal
Science advances, v.9, no.47
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Abstract
Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.
URI
https://pr.ibs.re.kr/handle/8788114/14722
DOI
10.1126/sciadv.adi8454
ISSN
2375-2548
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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